The goal of the Kerala Einstein study is to foster collaborative research to study risk factors for cognitive decline among older adults living in the southern Indian state of Kerala. Our research sites are the cities of Kozhikode and Thiruvananthapuram in Kerala state. The proposal will be directed by Dr Verghese, a neurologist at the Albert Einstein College of Medicine and a native of Kerala in collaboration with Dr. Mathuranath, Director, Division of Behavioral Neurology at the Sri Chitra Tirunal Institute, Thiruvananthapuram, one of India's premier postgraduate medical institutes. We now propose a more extensive RO1 grant propose leveraging the resources and collaborations successfully developed in our two-year R21 planning grant (R21 AGO29799) to study specific causes of cognitive decline in Kerala identified through our pilot research and to continue to provide training opportunities and build research capacity. Sociodemographic changes in Kerala in recent decades have created major lifestyle changes that have resulted in a cardiovascular disease epidemic as well as increased risk for dementia. We propose to examine the role of three potentially modifiable healthy lifestyle variables (diet, physical activity, and social networks) of high relevance to India that may prevent cognitive decline via their effects on cardiovascular, stress, inflammation, and other pathways in 1700 older adults participating in our longitudinal cohort study in Thiruvananthapuram over a two-year follow-up period (Aim 1). Cardiovascular disease causes both macrovascular (strokes) and microvascular brain damage that may contribute to cognitive decline. However, the role of microvascular disease (microbleeds, lacunar infarctions and leukoariaosis) in dementia is not well defined. Hence, we also propose to conduct a neuroimaging substudy to identify the behavioral correlates of microvascular disease in 75 subjects with amnestic Mid Cognitive Impairment syndrome and 150 healthy controls (Aim 2). Our studies have the potential to have a major impact in building sustainable research capacity in India, ultimately leading to the development of treatment and prevention strategies that are applicable worldwide. Defining role of healthy lifestyle factors and microvascular disease in Kerala may also help in understanding the parallel epidemic of cardiovascular disease and dementia in immigrant and minority populations who comprise a third of the US population. Our collaborators and their institutions are actively involved in formulating treatment and prevention policies locally and nationally, which will help take our findings from research settings to the community in India. PUBLIC HEALTH RELEVANCE: The Kerala-Einstein study aims to foster collaborative research between US and Indian investigators to study potentially modifiable risk factors for cognitive decline such as diet, physical activity, social networks, and vascular diseases among older adults living in the Indian state of Kerala. Our studies have the potential to have a major impact in building sustainable research capacity in India, ultimately lead to development of treatment and prevention strategies that are applicable worldwide.